Patient characteristics affecting knowledge of the possibility of surgical reconstruction for rheumatoid hand and wrist deformities.
We aimed to investigate patient characteristics affecting their knowledge of surgical reconstruction for rheumatoid hand and wrist deformities, and to investigate such characteristics affecting their hope of receiving hand surgery if patients with rheumatoid arthritis (RA) knew surgical reconstruction options. We carried out a questionnaire survey for all patients with RA who came to our outpatient department of rheumatology. Multivariate logistic regression analysis was performed to examine significant characteristics associated with the knowledge of surgical reconstruction and patients' hope of receiving hand surgery. In total, 687 patients were evaluated in this study and 337 (49%) reported knowledge about surgical reconstruction. A multivariate logistic regression analysis showed that patients with good control of disease activity and with long-lasting hand and wrist deformities were significantly associated with having knowledge of surgical reconstruction. Among the 337 patients with knowledge, only 122 (36%) expressed a hope of receiving hand surgery. The statistical analysis showed that younger age and surgical history were significantly associated with the hope of receiving surgery. Surgeons and rheumatologists should enlighten patients about the importance of hand surgery to achieve functional remission in this new era of treatment for patients with RA.


Acute effects of cocaine on anterior pituitary hormones in male and female rhesus monkeys.
The effects of acute cocaine administration (0.4 or 0.8 mg/kg) on anterior pituitary hormones were studied in four male and six female adult rhesus monkeys during the midluteal phase of the menstrual cycle (days 20-23). Progesterone levels averaged 15.7 +/- 3 and 10.6 +/- 2.8 ng/ml before low and high dose cocaine administration. Integrated plasma samples were collected every 10 min for 40 min before i.v. administration of cocaine, and 11 postcocaine samples were collected over 110 min. Cocaine (0.8 mg/kg) stimulated a significant increase in luteinizing hormone (LH) within 10 to 20 min (P < .01) and LH reached peak levels (59-60% above base line) within 30 min after cocaine administration in both males and females. Plasma cocaine levels averaged 289 +/- 23 and 346 +/- 73 ng/ml at 10 min after i.v. cocaine (0.8 mg/kg) administration in males and females, respectively. Follicle stimulating hormone levels were unchanged in midluteal females. Male testosterone increased by 50% above average base-line levels 50 min after the LH peak (80 min postcocaine). These data are consistent with our previous findings that cocaine increased LH and enhanced luteinizing hormone-releasing hormone-stimulated LH in early follicular females. The low dose of cocaine did not change basal levels of LH and follicle stimulating hormone in midluteal females and both LH and testosterone were unaffected in males. Cocaine plasma levels averaged 97.6 +/- 29 and 68.3 +/- 9.1 ng/ml at 10 min after 0.4 mg/kg of cocaine in males and females, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Poor semen quality may contribute to recent decline in fertility rates.
During past decades, we have witnessed a remarkable decline in fertility rates (number of births per 1000 women of reproductive age) in the industrialized world. It seems beyond doubt that the enormous social changes of our societies play the major role in this decline, but can it be attributed to changing social structures alone or is a reduced fecundity in the population also a factor? To address this we have focused on trends in teenage pregnancies (which to a large extent are unplanned). During the period in question fertility rates among 15-19 year old Danish women have been falling and the decline in fertility rate is not counterbalanced by an increase in the rate of induced abortion. When seen together with recent results from Denmark, which have shown that more than 30% of 19 year old men from the general population now have sperm counts in the subfertile range, we argue that this fall may not be attributable to social factors, changes in conception practices or diminished sexual activity alone. It seems reasonable also to consider widespread poor semen quality among men as a potential contributing factor to low fertility rates among teenagers. Due to the concern caused by the low sperm count among younger Danish men, the Danish Ministries of Health and Environment have launched a surveillance programme which includes an annual examination of the semen quality in 600 young Danes from the general population. We propose that researchers in other countries with low and falling fertility rates among young women should consider the possibility that semen quality of their younger male cohorts may also have deteriorated.


Manifest interstitial and vascular pathology in anti-neutrophil cytoplasmic antibody-associated renal disease.
Rapidly progressive renal failure in anti-neutrophil cytoplasmic antibody (ANCA)- associated renal disease customarily implies crescentic glomerulonephritis with approximately 50% of the glomeruli will have crescents. The tubulointerstitial inflammation is often proportionate to the glomerular inflammation and may have granulomatous pattern adjacent to the glomeruli or an inflamed vessel. A 77-year-old male with rapidly progressive renal failure was myeloperoxidase-ANCA positive, and renal histopathology revealed thrombotic microangio-pathy, significant interstitial inflammation, interstitial granulomas, and arteritis. Pathology is unique for the paucity of the classical crescents and the myriad of extraglomerular features. His renal function improved and stabilized after induction with cyclophosphamide and maintenance with azathioprine.


Unobserved heterogeneity in trauma patients' desire for autonomy in medical decision making in an emergency department.
To evaluate unobserved heterogeneity in trauma patients' desire for autonomy in medical decision making (DAD). This cross-sectional study at an inner-city emergency department screened 1009 patients for DAD (using the Decision Making Preference Scale of the Autonomy Preference Index), education level, and substance use. To investigate unobserved heterogeneity, a covariate adjusted finite mixture model was established. Model fit was evaluated with the Bayesian Information Criterion. The median age of participants was 32 years (range, 18-84 years) and 62% were male. Unobserved heterogeneity explained more variance in DAD than did sex, age, or substance use, but less variance than level of education. The best overall model fit was found with 3 latent subpopulations: 53.3% of patients with low DAD, 35.6% of patients with medium DAD, and 11.1% of patients with high DAD. Female sex and level of education showed a positive association; higher age and substance use showed a negative association with patients' DAD. Apart from a negative association with substance use and the known associations with sex and level of education, trauma patients' DAD showed substantial variability between individuals, and this variability could not be explained by these factors.


Idiopathic Interstitial Pneumonia Associated With Autoantibodies: A Large Case Series Followed Over 1 Year.
Some patients with autoimmune characteristics and idiopathic interstitial pneumonia, particularly usual interstitial pneumonia (UIP), do not fit neatly into the category of connective tissue disease-associated interstitial lung disease (CTD-ILD), idiopathic pulmonary fibrosis (IPF), or recently proposed yet to be validated criteria for interstitial pneumonia with autoimmune features (IPAF). Outcomes of these patients are unknown. This was a retrospective single-center study. Analyses of variance compared differences in mean change in FVC and diffusion capacity (Dlco) over 1 year among 124 well-defined patients (20 patients with positive autoantibodies with or without symptoms of connective tissue disease [AI-ILD], 15 patients with IPAF, 36 patients with CTD-ILD, and 53 patients with IPF with negative CTD serologies [Lone-IPF]). Of the patients, 75% with AI-ILD, 33% with IPAF, and 33% with CTD-ILD had UIP. Initial FVC and Dlco were similarly moderately reduced across groups. Mean change in FVC over 12 months was as follows: -60 mL (IPAF), -110 mL (AI-ILD), -10 mL (CTD-ILD), and -90 mL (Lone-IPF) (P = .52). Mean change in Dlco was as follows: 2.39 mL/mm Hg/min (IPAF), -1.15 mL/mm Hg/min (AI-ILD), -0.27 mL/mm Hg/min (CTD-ILD), and -1.05 mL/mm Hg/min (Lone-IPF) (P < .001). By pattern of disease, the mean change in FVC was as follows: -140 mL (UIP), 10 mL (nonspecific interstitial pneumonia), and 12 mL (unclassifiable/other) (P = .001). No clinically significant differences in pulmonary function to distinguish between patients with AI-ILD, IPAF, CTD-ILD, and Lone-IPF were observed after 1 year. Longer periods of follow-up are needed to understand the outcomes of these patients. It is not yet clear whether AI-ILD is a distinct phenotype or a variant of the newly proposed entity IPAF.


Information and communication technology in disease surveillance, India: a case study.
India has made appreciable progress and continues to demonstrate a strong commitment for establishing and operating a disease surveillance programme responsive to the requirements of the International Health Regulations (IHR[2005]). Within five years of its launch, India has effectively used modern information and communication technology for collection, storage, transmission and management of data related to disease surveillance and effective response. Terrestrial and/or satellite based linkages are being established within all states, districts, state-run medical colleges, infectious disease hospitals, and public health laboratories. This network enables speedy data transfer, video conferencing, training and e-learning for outbreaks and programme monitoring. A 24x7 call centre is in operation to receive disease alerts. To complement these efforts, a media scanning and verification cell functions to receive reports of early warning signals. During the 2009 H1N1 outbreak, the usefulness of the information and communication technology (ICT) network was well appreciated. India is using ICT as part of its Integrated Disease Surveillance Project (IDSP) to help overcome the challenges in further expansion in hard-to-reach populations, to increase the involvement of the private sector, and to increase the use of other modes of communication like e-mail and voicemail.


Vernet syndrome by varicella-zoster virus.
Vernet syndrome involves the IX, X, and XI cranial nerves and is most often attributable to malignancy, aneurysm or skull base fracture. Although there have been several reports on Vernet's syndrome caused by fracture and inflammation, cases related to varicella-zoster virus are rare and have not yet been reported in South Korea. A 32-year-old man, who complained of left ear pain, hoarse voice and swallowing difficulty for 5 days, presented at the emergency room. He showed vesicular skin lesions on the left auricle. On neurologic examination, his uvula was deviated to the right side, and weakness was detected in his left shoulder. Left vocal cord palsy was noted on laryngoscopy. Antibody levels to varicella-zoster virus were elevated in the serum. Electrodiagnostic studies showed findings compatible with left spinal accessory neuropathy. Based on these findings, he was diagnosed with Vernet syndrome, involving left cranial nerves, attributable to varicella-zoster virus.


Identification of human papillomavirus 16-E6 protein-derived peptides with the potential to generate cytotoxic T-lymphocytes toward human leukocyte antigen-A24+ cervical cancer.
Human papillomavirus 16 (HPV16)-E6 and -E7 proteins are considered to be appropriate targets in specific immunotherapy for cervical cancer. In this study, we attempted to identify epitope peptides from the HPV16-E6 protein that have the potential to generate cytotoxic T-lymphocytes (CTLs) toward human leukocyte antigen (HLA)-A24+ cervical cancer. Two HPV16-E6 peptides at positions 75-83 and 91-100 effectively induced peptide-specific CTLs from peripheral blood mononuclear cells of HLA-A24+ cervical cancer patients. These HPV16-E6 peptide-induced CTLs showed cytotoxicity against HLA-A24+ and HPV16-E6 protein-expressing cervical cancer cells. Experiments with blocking antibodies and cold inhibition targets revealed that the cytotoxicity was mainly dependent on peptide-specific and CD8+ T cells. In addition, based on our observation that induction of immunoglobulin G (IgG) reactive to administered CTL-directed peptides is correlated with clinical responses, we attempted to detect IgG reactive to HPV16-E6 peptides in the plasma of cancer patients. As a result, IgGs reactive to the HPV16-E691-100 peptide were detected in 4 of 12 cervical cancer patients. These results indicate that these HPV16-E6-derived peptides are good candidates in peptide-based immunotherapy for HLA-A24+ cervical cancer patients.


Associations of Recreational and Nonrecreational Physical Activity and Body Weight Change on Cardiovascular Disease Mortality During the Obesogenic Transition in the United States: National Health and Nutrition Examination Survey Follow-up Study.
To investigate cardiovascular disease mortality associated with longitudinal changes in body weight, and recreational and nonrecreational physical activity during the obesogenic transition in the United States since the 1970s. Data were analyzed from 4921 individuals aged 25-74 years who participated in the National Health and Nutrition Examination Survey between 1971 and 1979 and follow-up studies to 1992. Mortality was confirmed by searching the National Death Index or proxy interview; clinical data were collected in person. Changes in self-reported recreational and nonrecreational physical activity categories over time were coded as stable, increase, or decrease. Competing risks regression was used to determine hazard ratios adjusted for covariates. A logit model in a generalization method was used to explore mediation effects of change in body weight. Compared with the "moderate-vigorous stable" group (reference), individuals who remained inactive ("inactive stable") or reduced their participation in physical activity ("active to inactive") experienced the highest mortality, with a 50% to 176% and 22% to 222% relative increased hazard ratios for nonrecreational and recreational physical activity, respectively, across all models adjusted for covariates. This corresponded to significant loss of life (up to 3 y; all P < .05). Individuals who became active ("inactive to active") were not at increased risk. We found weak (but nonstatistically significant) evidence of mediation effects of body weight change on mortality. Longitudinal changes in moderate-vigorous recreational and nonrecreational physical activity were important predictors of cardiovascular disease mortality during the obesogenic transition period in the United States and were mostly unexplained by changes in body weight.


Functional analysis of the C2A domain of synaptotagmin 1: implications for calcium-regulated secretion.
Synaptotagmin 1 is proposed to function as a low affinity calcium sensor for calcium-triggered exocytosis from neural and neuroendocrine cells. Because of the calcium-binding properties of the C2A domain of synaptotagmin 1, calcium-dependent interactions through this domain may modulate neurotransmitter release. We addressed this question by using alanine-scanning mutagenesis to generate a series of mutations within the C2A domain of synaptotagmin 1. The effects of these mutations on synaptotagmin 1 C2A function were analyzed for (1) calcium-dependent phospholipid binding, (2) calcium-dependent binding to syntaxin 1A, a plasma membrane protein critical for vesicle docking or fusion, and (3) calcium-regulated secretion after microinjection into neuroendocrine pheochromocytoma (PC12) cells. Our analyses reveal that a polylysine motif at residues 189-192 confers an inhibitory effect on secretion by recombinant synaptotagmin C2A fragments. The synaptotagmin 1 C2A polylysine motif functions independently of calcium-mediated interactions with phospholipids and syntaxin 1A. Furthermore, alpha-latrotoxin reverses the inhibitory effect of injected recombinant C2A fragments, suggesting that they perturb the cellular calcium-sensing machinery by interfering with synaptotagmin 1 activity in vivo. Our results indicate that novel calcium-independent interactions mediated through the C2A polylysine motif of synaptotagmin 1 function to modulate neurotransmitter release.


Genetic analysis of noroviruses in Chiba Prefecture, Japan, between 1999 and 2004.
Noroviruses (NVs) are common pathogens that consist of genetically divergent viruses that induce gastroenteritis in humans and animals. Between September 1999 and June 2004, 1,898 samples obtained from patients showing sporadic or outbreak gastroenteritis in Chiba Prefecture, Japan, were tested for NVs by reverse transcription-PCR. NVs were detected in 603 samples. Approximately 80% were positive for genogroup GII, 13% were positive for genogroup GI, and the remaining 7% were positive for both genogroups. Phylogenetic analysis showed that the GI and GII genogroups could be further divided into 13 and 16 genotypes (including new genotypes), respectively. The GII-4 genotype, which included five small genetic clusters (subtypes), was the most common in this study and was detected in approximately 40% of positive samples. The P2 regions of 10 strains belonging to each of the five GII-4 subtypes showed 5 to 18% amino acid diversity. The amino acid substitutions accumulated in the protruding (P) region during the 5-year study period. Our data suggest that highly variable NV strains are circulating in Chiba Prefecture, with a high rate of genetic change observed during the 5-year study period.


Experience with epigastric free flap transfer in the rat: technique and results.
We have described the advantages and disadvantages of using the rat epigastric free flap as a means of studying transplantation phenomena. The study comprises 20 epigastric free flap autografts in rats. After 1 1/2 years of working on the model, we achieved a 75% success rate in the last 20 consecutive procedures. From our experience with this model, we feel that the rat epigastric flap has a place in the study of transplantation phenomena in the experimental laboratory. In addition, we feel that this is an excellent technical exercise for maintaining proficiency in performing microvascular anastomoses.


Kinetic Analysis for High-Temperature Coarsening of γ″ Phase in Ni-Based Superalloy GH4169.
The growth of precipitates in Ni-based superalloy GH4169 is critical as it controls the mechanical properties and long-term stability of the alloy. In this paper, the coarsening behavior of the main strengthening phase γ″ in the temperature range from 800 °C to 900 °C is investigated. Two heat treatment steps, i.e., pre-precipitation of γ″ phase and coarsening of precipitates at high temperatures, were performed on the GH4169 alloy. It was found that there were three morphological forms of γ″ phase in chronological order: lip-shape, disc-shape, and irregular rectangle-shape with larger size. The coarsening kinetics of γ″ phase followed the Lifshitz-Slyozov-Wagner (LSW) time-law for diffusion-controlled growth, and the activation energies of γ″ phase before and after losing the coherent relationship with matrix were 261 kJ mol-1 and 271 kJ mol-1, respectively.


RABiT-II: A Fully-Automated Micronucleus Assay System with Shortened Time to Result.
In this work, we describe a fully automated cytokinesis-block micronucleus (CBMN) assay with a significantly shortened time to result, motivated by the need for rapid high-throughput biodosimetric estimation of radiation doses from small-volume human blood samples. The Rapid Automated Biodosimetry Tool (RABiT-II) currently consists of two commercial automated systems: a PerkinElmer cell::explorer Workstation and a GE Healthcare IN Cell Analyzer 2000 Imager. Blood samples (30 μl) from eight healthy volunteers were gamma-ray irradiated ex vivo with 0 (control), 0.5, 1.5, 2.5, 3.5 or 4.5 Gy and processed with full automation in 96-well plates on the RABiT-II system. The total cell culture time was 54 h and total assay time was 3 days. DAPI-stained fixed samples were imaged on an IN Cell Analyzer 2000 with fully-automated image analysis using the GE Healthcare IN Cell Developer Toolbox version 1.9. A CBMN dose-response calibration curve was established, after which the capability of the system to predict known doses was assessed. Various radiation doses for irradiated samples from two donors were estimated within 20% of the true dose (±0.5 Gy below 2 Gy) in 97% of the samples, with the doses in some 5 Gy irradiated samples being underestimated by up to 25%. In summary, the findings from this work demonstrate that the accelerated CBMN assay can be automated in a high-throughput format, using commercial biotech robotic systems, in 96-well plates, providing a rapid and reliable bioassay for radiation exposure.


Primary acquired nasolacrimal duct obstruction: is it really related to paranasal abnormalities?
To investigate whether there is an association between primary acquired nasolacrimal duct obstruction and paranasal computed tomography (CT) findings. The study cohort consisted of paranasal CT images from 40 patients being treated for unilateral primary nasolacrimal duct obstruction (PANDO) and the reformatted coronal temporal CT images of 71 control subjects who attended the ENT clinic with the complaint of vertigo and tinnitus. A radiologist masked to the clinical situation of participants, investigated the paranasal CT findings of the PANDO and control patients retrospectively. The side, localization, and angle of the septal deviation as well as the thickness and lateralization angle of the inferior turbinate's were recorded. Additionally maxillary and ethmoid sinusitis, concha bullosa, Agger nasi cell formation, and osteomeatal complex status were evaluated. No significant difference was found between the paranasal abnormality incidence in the PANDO and non-PANDO sides of the patients or the control group. Only the side of the septal deviation correlated with the side of the PANDO (p = 0.008). The incidence of PANDO may not be directly related to paranasal abnormalities. Further large-scale studies should be performed to clarify the relationship between paranasal abnormalities and PANDO.


Differences in macrophage activation by bacterial DNA and CpG-containing oligonucleotides.
Bacterial DNA activates mouse macrophages, B cells, and dendritic cells in a TLR9-dependent manner. Although short ssCpG-containing phosphodiester oligonucleotides (PO-ODN) can mimic the action of bacterial DNA on macrophages, they are much less immunostimulatory than Escherichia coli DNA. In this study we have assessed the structural differences between E. coli DNA and PO-ODN, which may explain the high activity of bacterial DNA on macrophages. DNA length was found to be the most important variable. Double-strandedness was not responsible for the increased activity of long DNA. DNA adenine methyltransferase (Dam) and DNA cytosine methyltransferase (Dcm) methylation of E. coli DNA did not enhance macrophage NO production. The presence of two CpG motifs on one molecule only marginally improved activity at low concentration, suggesting that ligand-mediated TLR9 cross-linking was not involved. The major contribution was from DNA length. Synthetic ODN >44 nt attained the same levels of activity as bacterial DNA. The response of macrophages to CpG DNA requires endocytic uptake. The length dependence of the CpG ODN response was found to correlate with the presence in macrophages of a length-dependent uptake process for DNA. This transport system was absent from B cells and fibroblasts.


An anatomical study of Morton's interdigital neuroma: the relationship between the occurring site and the deep transverse metatarsal ligament (DTML).
Using clinical and cadaver studies, we examined the relationship between the location of Morton interdigital neuromas and the surrounding structures, including the deep transverse metatarsal ligament (DTML), which has been suspected as a major causative factor in neuroma formation. Seventeen fresh-frozen cadavers were evaluated to determine the relationship between the location of Morton interdigital neuromas and the DTML at two phases of the gait cycle with 60 degrees of metatarsophalangeal dorsiflexion and with 15 degrees of ankle dorsiflexion. We measured the distance from the bifurcation of the common digital nerve in the foot to the anterior margin of the DTML and also measured the length of the DTML itself. Clinically, we checked the location of the Morton interdigital neuroma and its length during surgery in 32 feet. In the second and third webspace, the mean distance from the bifurcation of the common digital nerve of the foot to the anterior margin of the DTML was 16.7 mm, 15.1 mm in the mid-stance position, and 15.9 mm and 14.6 mm in the heel-off position. The length of the second and third DTML averaged 12.8 mm and 10.6 mm. Clinically, all of the cases of Morton interdigital neuroma started at the bifurcation area of the common digital nerve, and the mean neuroma length was 7.5 mm (6 to 11). Morton interdigital neuromas were located more distally than the DTML in both the mid-stance and the heel-off stage during walking. The main lesion was located between the metatarsal head and the metatarsophalangeal joint and more distal than the DTML, questioning previous studies suggesting that the DTML is the major causative factor in development of Morton interdigital neuroma.


[Multiple anomalies of cerebral vessels. A case of multiple aneurysms associated with fenestration of the middle cerebral artery and persistent primitive trigeminal artery].
A case of multiple intracranial anomalies was reported. They consisted of fenestration of the middle cerebral artery (MCA), persistent primitive trigeminal artery and four intracranial aneurysms. The patient, 45-year-old male, had an attack of subarachnoid hemorrhage on July 15, 1982. He was transferred and admitted to our Dept. of Neurosurgery on July 27. On admission neurological examinations revealed retinal hemorrhage, bilateral papilledema and abducens nerve paresis on the left. Cerebral angiography demonstrated multiple aneurysms, one in the left vertebral artery, one in the left MCA, one in the right IC-PC junction and one in the fenestrated right MCA and persistent primitive trigeminal artery. Computed tomography (CT) demonstrated high density areas in the basal cistern and bilateral sylvian fissures, and cavum septi pellucidi and cavum Vergae as well. Surgical intervention was done and all aneurysms were clipped or coated successfully. The aneurysm in the fenestrated right MCA had originated from the proximal end of the fenestration of the MCA. The cavum septi pellucidi and cavum Vergae were asymptomatic. The postoperative course was uneventful. The authors discussed the pathogenesis and clinical meanings of fenestration of the MCA and persistent primitive trigeminal artery, and inferred that the genetic abnormality at the stage of development of cerebral vessels could play one part of the formation of intracranial aneurysms, because of the fact that the cerebrovascular anomalies showed high incidence of coexistence of intracranial aneurysms.


Controlled study of self-exposure treatment for phobics: preliminary communication.
Patients with phobic disorder (mainly agoraphobics ) of minimum one year duration were treated by self-administered exposure in vivo treatment. Seventy-one patients were randomly assigned to one of three groups: (A) book-instructed, (B) computer-instructed, or (C) therapist-instructed. All three groups improved significantly to a similar extent on various phobic measures at the end of the treatment and maintained their treatment gains at 6-month follow up. Mean clinicians' time spent with each patient was 40 minutes, 4.2 hours and 3.2 hours in group A, B and C respectively. Similar small numbers of patients defaulted from each group.


IK-DDI: a novel framework based on instance position embedding and key external text for DDI extraction.
Determining drug-drug interactions (DDIs) is an important part of pharmacovigilance and has a vital impact on public health. Compared with drug trials, obtaining DDI information from scientific articles is a faster and lower cost but still a highly credible approach. However, current DDI text extraction methods consider the instances generated from articles to be independent and ignore the potential connections between different instances in the same article or sentence. Effective use of external text data could improve prediction accuracy, but existing methods cannot extract key information from external data accurately and reasonably, resulting in low utilization of external data. In this study, we propose a DDI extraction framework, instance position embedding and key external text for DDI (IK-DDI), which adopts instance position embedding and key external text to extract DDI information. The proposed framework integrates the article-level and sentence-level position information of the instances into the model to strengthen the connections between instances generated from the same article or sentence. Moreover, we introduce a comprehensive similarity-matching method that uses string and word sense similarity to improve the matching accuracy between the target drug and external text. Furthermore, the key sentence search method is used to obtain key information from external data. Therefore, IK-DDI can make full use of the connection between instances and the information contained in external text data to improve the efficiency of DDI extraction. Experimental results show that IK-DDI outperforms existing methods on both macro-averaged and micro-averaged metrics, which suggests our method provides complete framework that can be used to extract relationships between biomedical entities and process external text data.


Transition metal-catalyzed ring-opening polymerization (ROP) of strained, silicon-bridged bis(benzene)chromium complexes.
Silicon-bridged bis(benzene)chromium complexes (sila[1]chromarenophanes) undergo facile transition metal-catalyzed ROP at ambient temperature in the presence of Karstedt's catalyst to yield polychromarenylsilanes, the first homopolymers with main chains of Cr(arene)(2) and organosilane units.


[Gaseous Nitrogen Emission from Soil After Application of NH4+-N Loaded Biochar].
To safely and effectively transfer NH4+-N from eutrophic water to soil, biochar was applied to adsorb NH4+-N from wastewater, and this NH4+-N loaded biochar (N-BC) was subsequently used as a soil amendment. Understanding the influence of N-BC on N2O-N emission and NH3-N volatilization is important for both decreasing the application of chemical fertilizers and reducing gaseous nitrogen loss from soil. In this study, experiments were conducted in soil columns with four treatments, namely CK (no fertilizer), NPK (chemical fertilizer), N-BC+PK (NH4+-N loaded biochar+chemical fertilizer), and BC+NPK (biochar+chemical fertilizer). Compared to both the NPK and BC+NPK treatments, N-BC+PK significantly reduced the cumulative N2O-N emissions and NH3-N volatilization, as well as the total gaseous nitrogen loss from the soil (P<0.05). Relative to NPK and BC+NPK, cumulative N2O-N emissions decreased by 33.62% and 24.64%, cumulative NH3-N volatilization decreased 70.64% and 79.29%, and the cumulative total gaseous nitrogen loss decreased by 64.97% and 73.75%. In particular, BC+NPK significantly enhanced the cumulative NH3-N volatilization. Furthermore, the N2O-N emission flux and NH3-N volatilization rate were significantly positively correlated with the NH4+-N concentration, NO3--N concentration, and pH of soil (P<0.01). Overall, using NH4+-N loaded biochar can significantly decrease N2O-N emissions and NH3-N volatilization, relative to the traditional application combining biochar and chemical fertilizer. This research provides solid theoretical support and data for the application of NH4+-N loaded biochar in soil, to reduce gaseous nitrogen loss.


Trust in health information websites: A systematic literature review on the antecedents of trust.
Health websites are important sources of information for consumers. In choosing websites, trust in websites largely determines which website to access and how to best utilize the information. Thus, it is critical to understand why consumers trust certain websites and distrust others. A systematic literature review was conducted with the goal of identifying the antecedents of trust in health information websites. After four rounds of screening process, 20 articles between 2000 and 2013 were harvested. Factors that determine trust are classified into individual difference antecedents, website-related antecedents, and consumer-to-website interaction-related antecedents. The most frequently studied antecedents were socio-demographics, information quality, appearance, and perceived reputation of the website. Each antecedent of trust are discussed in detail and future research directions are proposed.


The identification and characterization of osmotolerant yeast isolates from chemical wastewater evaporation ponds.
Ramat Hovav is a major chemical industrial park manufacturing pharmaceuticals, pesticides, and various aliphatic and aromatic halogens. All wastewater streams are collected in large evaporation ponds. Salinity in the evaporation ponds fluctuates between 3% (w/v) and saturation and pH values range between 2.0 and 10.0. We looked for microorganisms surviving in these extreme environmental conditions and found that 2 yeast strains dominate this biotope. 18S rDNA sequence analysis identified the isolates as Pichia guilliermondii and Rhodotorula mucilaginosa. Both isolates grew in NaCl concentrations ranging up to 3.5 M and 2.5 M, respectively, and at a pH range of 2-10. There was a distinct difference between the Rhodotorula and Pichia strains and S. cerevisiae RS16 that served as a control strain with respect to accumulation of osmoregulators and internal ion concentrations when exposed to osmotic stress. The Pichia and Rhodotorula strains maintained high glycerol concentration also in media low in NaCl. Utilization of various carbon sources was examined. Using a tetrazolium-based assay we show that the Rhodotorula and Pichia strains are capable of utilizing a wide range of different carbon sources including anthracene, phenanthrene, and other cyclic aromatic hydrocarbons.


Identification of NURR1 (Exon 4) and FOXA1 (Exon 3) Haplotypes Associated with mRNA Expression Levels in Peripheral Blood Lymphocytes of Parkinson's Patients in Small Indian Population.
Here, we study the expression of NURR1 and FOXA1 mRNA in peripheral blood lymphocytes and its haplotypes in coding region in a small Chennai population of India. Thirty cases of Parkinson's patients (PD) with anti-PD medications (20 males aged 65.85 ± 1.19 and 10 females aged 65.7 ± 1.202) and 30 age matched healthy people (20 males aged 68.45 ± 1.282 and 10 females aged 65.8 ± 1.133) were included. The expression of NURR1 and FOXA1 in PBL was detected by Q-PCR and haplotypes were identified by PCR-SSCP. In the 30 PD cases examined, NURR1 and FOXA1 expression was significantly reduced in both male and female PD patients. However, NURR1 (57.631% reduced in males; 28.93% in females) and FOXA1 (64.42% in males; 55.76% in females) mRNA expression did differ greatly between male and female PD patients. Polymorphisms were identified at exon 4 of the NURR1 and at exon 3 of the FOXA1, respectively, in both male and female patients. A near significant difference in SSCP patterns between genders of control and PD population was analyzed suggesting that further investigations of more patients, more molecular markers, and coding regions should be performed. Such studies could potentially reveal peripheral molecular marker of early PD and different significance to the respective genders.


Neuregulin-1β induces proliferation, survival and paracrine signaling in normal human cardiac ventricular fibroblasts.
Neuregulin-1β (NRG-1β) is critical for cardiac development and repair, and recombinant forms are currently being assessed as possible therapeutics for systolic heart failure. We previously demonstrated that recombinant NRG-1β reduces cardiac fibrosis in an animal model of cardiac remodeling and heart failure, suggesting that there may be direct effects on cardiac fibroblasts. Here we show that NRG-1β receptors (ErbB2, ErbB3, and ErbB4) are expressed in normal human cardiac ventricular (NHCV) fibroblast cell lines. Treatment of NHCV fibroblasts with recombinant NRG-1β induced activation of the AKT pathway, which was phosphoinositide 3-kinase (PI3K)-dependent. Moreover, the NRG-1β-induced PI3K/AKT signaling in these cells required phosphorylation of both ErbB2 and ErbB3 receptors at tyrosine (Tyr)1248 and Tyr1289 respectively. RNASeq analysis of NRG-1β-treated cardiac fibroblasts obtained from three different individuals revealed a global gene expression signature consistent with cell growth and survival. We confirmed enhanced cellular proliferation and viability in NHCV fibroblasts in response to NRG-1β, which was abrogated by PI3K, ErbB2, and ErbB3 inhibitors. NRG-1β also induced production and secretion of cytokines (interleukin-1α and interferon-γ) and pro-reparative factors (angiopoietin-2, brain-derived neurotrophic factor, and crypto-1), suggesting a role in cardiac repair through the activation of paracrine signaling.


Spatial diversity of bacterioplankton communities in surface water of northern South China Sea.
The South China Sea is one of the largest marginal seas, with relatively frequent passage of eddies and featuring distinct spatial variation in the western tropical Pacific Ocean. Here, we report a phylogenetic study of bacterial community structures in surface seawater of the northern South China Sea (nSCS). Samples collected from 31 sites across large environmental gradients were used to construct clone libraries and yielded 2,443 sequences grouped into 170 OTUs. Phylogenetic analysis revealed 23 bacterial classes with major components α-, β- and γ-Proteobacteria, as well as Cyanobacteria. At class and genus taxon levels, community structure of coastal waters was distinctively different from that of deep-sea waters and displayed a higher diversity index. Redundancy analyses revealed that bacterial community structures displayed a significant correlation with the water depth of individual sampling sites. Members of α-Proteobacteria were the principal component contributing to the differences of the clone libraries. Furthermore, the bacterial communities exhibited heterogeneity within zones of upwelling and anticyclonic eddies. Our results suggested that surface bacterial communities in nSCS had two-level patterns of spatial distribution structured by ecological types (coastal VS. oceanic zones) and mesoscale physical processes, and also provided evidence for bacterial phylogenetic phyla shaped by ecological preferences.


Oxidative Stress Impairs Fatty Acid Oxidation and Mitochondrial Function in the Term Placenta.
Placental fatty acid oxidation (FAO) is impaired and lipid storage is increased in pregnancy states associated with chronic oxidative stress. The effect of acute oxidative stress, as seen in pregnancies complicated with asthma, on placental lipid metabolism is unknown. We hypothesized that induction of acute oxidative stress would decrease FAO and increase esterification. We assessed [3H]-palmitate oxidation and esterification in term placental explants from lean women after exposure to hydrogen peroxide (H2O2) for 4 hours. Fatty acid oxidation decreased 16% and 24% in placental explants exposed to 200 (P = .02) and 400 µM H2O2 (P = .01), respectively. Esterification was not altered with H2O2 exposure. Neither messenger RNA nor protein expression of key genes involved in FAO (eg, peroxisome proliferator-activated receptor α, carnitine palmitoyl transferase 1b) were altered. Adenosine triphosphate (ATP) levels decreased with induction of oxidative stress, without increasing cytotoxicity. Acute oxidative stress decreased FAO and ATP production in the term placenta without altering fatty acid esterification. As decreases in placental FAO and ATP production are associated with impaired fetal growth, pregnancies exposed to acute oxidative stress may be at risk for fetal growth restriction.


Incorporation of stochastic engineering models as prior information in Bayesian medical device trials.
Evaluation of medical devices via clinical trial is often a necessary step in the process of bringing a new product to market. In recent years, device manufacturers are increasingly using stochastic engineering models during the product development process. These models have the capability to simulate virtual patient outcomes. This article presents a novel method based on the power prior for augmenting a clinical trial using virtual patient data. To properly inform clinical evaluation, the virtual patient model must simulate the clinical outcome of interest, incorporating patient variability, as well as the uncertainty in the engineering model and in its input parameters. The number of virtual patients is controlled by a discount function which uses the similarity between modeled and observed data. This method is illustrated by a case study of cardiac lead fracture. Different discount functions are used to cover a wide range of scenarios in which the type I error rates and power vary for the same number of enrolled patients. Incorporation of engineering models as prior knowledge in a Bayesian clinical trial design can provide benefits of decreased sample size and trial length while still controlling type I error rate and power.


Insulin promotes cell migration by regulating PSA-NCAM.
Cellular interactions with the extracellular environment are modulated by cell surface polysialic acid (PSA) carried by the neural cell adhesion molecule (NCAM). PSA-NCAM is involved in cellular processes such as differentiation, plasticity, and migration, and is elevated in Alzheimer's disease as well as in metastatic tumour cells. Our previous work demonstrated that insulin enhances the abundance of cell surface PSA by inhibiting PSA-NCAM endocytosis. In the present study we have identified a mechanism for insulin-dependent inhibition of PSA-NCAM turnover affecting cell migration. Insulin enhanced the phosphorylation of the focal adhesion kinase leading to dissociation of αv-integrin/PSA-NCAM clusters, and promoted cell migration. Our results show that αv-integrin plays a key role in the PSA-NCAM turnover process. αv-integrin knockdown stopped PSA-NCAM from being endocytosed, and αv-integrin/PSA-NCAM clusters co-labelled intracellularly with Rab5, altogether indicating a role for αv-integrin as a carrier for PSA-NCAM during internalisation. Furthermore, inhibition of p-FAK caused dissociation of αv-integrin/PSA-NCAM clusters and counteracted the insulin-induced accumulation of PSA at the cell surface and cell migration was impaired. Our data reveal a functional association between the insulin/p-FAK-dependent regulation of PSA-NCAM turnover and cell migration through the extracellular matrix. Most importantly, they identify a novel mechanism for insulin-stimulated cell migration.


Distinct Dynamics of Mitotic Transition in B-Cell Lymphoma and Reactive B-Cell Lymphoproliferations Determined by H3S10 Phosphohistone Immunolabeling.
Clonal selection in the follicular germinal centers in lymphatic tissues is accompanied by an intense proliferation of polyclonal B cells in a precisely regulated fashion. In contrast, B-cell neoplasias proliferate autonomously due to endogenous stimuli. The cell kinetic activity is obvious at many levels including progressive chromatin modification and elevated mitotic rates. We asked if there are differences in the kinetics of histone H3S10 phosphorylation required for mitotic entry between highly proliferating B cells of reactive germinal centers and in B-cell lymphomas with different proliferative capacity. Phospho-H3 histone (pH3S10)-specific immunohistochemistry was applied to cultivated cell, reactive and selected indolent and aggressive lymphoma samples (diffuse large B-cell lymphoma, Burkitt lymphoma, lymphoblastic lymphoma, follicular lymphoma and small lymphocytic lymphoma). Microscopic quantification of the "dot-type" (representing late G2 phase) and "mitotic" immunolabeling patterns per field of view was performed and compared with classical cell proliferation markers. In addition to the dense homogeneous chromatin labeling highlighting mitotic figures, we stated a selective dot-type nuclear labeling representing ongoing chromatin condensation in premitotic G2 phase cells. While cell proliferation and mitotic counts correlated in general with histology, statistical analysis indicated an accumulation of G2 phase pH3S10 pattern in the reactive germinal centers in contrast to lymphomas. The dot-type G2 staining pattern was surprisingly overrepresented (1,321.7 ± 356.5/10 HPF) in the reactive germinal centers compared to aggressive lymphomas (101.3 ± 33.1) (p < 0.005). The relative G2/M value was significantly higher (4.6 ± 0.6) in reactive germinal center B cells than in any lymphoma entity evaluated (0.7 ± 0.2 in Burkitt lymphoma, 0.9 ± 0.4 in grade 3b follicular lymphoma, 1.3 ± 1.1 in diffuse large B-cell lymphoma, 1.5 ± 0.6 in lymphoblastic lymphoma, and 0.9 ± 0.2 in small lymphocytic lymphoma). pH3S10 immunohistochemistry enabled the presentation of significant differences in the cell cycle kinetics between reactive and neoplastic B-cell lymphoproliferations. Accumulation of G2 phase B cells in reactive folliculi directs to physiological G2/M checkpoint blockade. In contrast, accelerated G2/M transition in lymphomas is potentially associated with impaired genomic repair and cell death mechanisms.


Multiple-echo proton spectroscopic imaging using time domain parametric spectral analysis.
A multiple-echo MR spectroscopic imaging (MRSI) method is presented that enables improved metabolite imaging in the presence of local field inhomogeneities and measurement of transverse relaxation parameters. Short echo spacing is used to maximize signal energy from inhomogeneously line-broadened resonances, and time domain parametric spectral analysis of the entire echo train is used to obtain sufficient spectral resolution from the shortened sampling periods. Optimal sequence parameters for 1H MRSI are determined by computer simulation, and performance is compared with conventional single-echo acquisition using phantom studies at a field strength of 4.7 T. A preliminary example for use at 1.5 T is also presented using phantom and human brain MRSI studies. This technique is shown to offer improved performance relative to single-echo MRSI for imaging of metabolites with shortened T2* values due to the presence of local field inhomogeneities. Additional advantages are the intrinsic measurement of metabolite T2 values and determination of metabolite integrals without T2 weighting, thereby facilitating quantitative metabolite imaging.


Sytematic review and meta-analysis of prevalence of hepatitis B in India.
To evaluate the point prevalence of Hepatitis B in India. Meta-analysis of data on point prevalence from different parts of the country. Searches were made in Medline, Cochrane Library and Best bets and previous reviews. A limited hand search of cross references was also done. Finally a consultation with experts was held to enlarge the references base. Studies reporting prevalence of HBsAg were selected. Data from high risk groups were excluded. 54 papers reporting data on 61 populations were identified. The true prevalence for each study was calculated from the reported prevalence using the specificity and sensitivity of the test employed. The true prevalence in non-tribal populations is 2.4% (95% CI: 2.2%-2.7%). True prevalence among tribal populations is 15.9% (CI: 11.4%-20.4%). These figures may be useful in estimation of the burden of the disease in the country and for projecting the cost-benefits of immunization.


CRISPR/Cas9-Enabled Multiplex Genome Editing and Its Application.
The CRISPR/Cas9 system is a prevalent and versatile genome-editing tool of choice for basic and applied biological research. An exchange of a 20-bp spacer sequence in the gRNA can easily reprogram Cas9 to target a different DNA site. By expressing or providing multiple gRNAs, the system also enables multiplex genome editing at high efficiencies. Current approaches for providing multiple gRNAs in vivo include the use of multigene cassettes to express several gRNAs, Csy4-based excision, arrays of crRNAs, ribozyme-flanked gRNAs, tRNA-dependent cleavage of gRNAs, and direct introduction of Cas9 proteins preloaded with different gRNAs. By simultaneously targeting multiple DNA sequences, multiplex genome editing can be used to knockout multiple genes or delete chromosomal fragments. Off-target risk can also be reduced by Cas9-dimers that require the simultaneous expression of two gRNAs. With multiple gRNAs, specific gene expression or methylation status can be efficiently controlled by dCas9 fused to activators, repressors, methyltransferase, demethylase, or other functional domains. As a result, multiplex genome editing is expected to accelerate functional discovery of plant genes as well as genetic improvement of agricultural crops.


Deep vein thrombosis: thrombolysis in the pediatric population.
Improved medical treatment options have advanced pediatric care but often necessitate both invasive vascular procedures and venous access predisposing these patients to venous thrombotic events. Although pediatric deep vein thrombosis (DVT) is an increasingly recognized phenomenon, high-quality evidence for its antithrombotic treatment in general remains limited, and even more so with respect to thrombolytic therapy. Correspondingly, current American College of Chest Physicians guidelines discourage the routine use of thrombolytic therapy for pediatric DVT; by contrast, American Heart Association guidelines suggest consideration for such therapy in young patients in whom the balance of benefit to risk may be most favorable. The developing hemostatic system and relative rarity of thrombotic events have historically posed impediments to the design and conduction of prospective clinical trials of thrombolysis in children. This narrative review summarizes available information regarding thrombolytic therapy for pediatric DVT.


A survey of nursing practice in the assessment and management of pain in children.
The purpose of this study was to describe nurses' perceptions of their practices in the assessment and management of pain in children. Questionnaires were distributed to 260 nurses in a pediatric hospital in the western United States. Results showed that nurses are not consistently assessing pain in children, and pain management practices are not based on systematic assessment. The most frequently reported tool for assessing pain was the numeric rating scale. Children experience a variety of painful procedures during hospitalization, but nurses reported that they are not consistently administering analgesics for painful procedures. Although rarely used, distraction and relaxation techniques were the most frequently reported nonpharmacological interventions. Although nurses did not feel that there were factors preventing them from assessing or managing pain in children, their practices revealed both that they are not using developmentally appropriate tools for assessing pain, and they have not maximized the use of management strategies for controlling pain.


Determination of elements in native and bypass human coronary artery plaque deposits from the same heart using inductively coupled plasma-mass spectrometry.
As part of an ongoing study on atherosclerotic arteries, the concentrations of 12 elements in a native and by-pass human coronary artery plaque deposits from five human hearts were determined using inductively coupled plasma-mass spectrometry (ICP-MS). These elements were Ca, P, Na, K, Mg, Zn, Cu, Pb, Fe, Al, Si, and S. For Zn, Ca, Pb, Fe, Al, and Si, the levels were at the fractional micromol/g levels and they probably played an unimportant role in plaque development. Sulfur levels varied from 23 to 140 micromols indicative of the possible presence of homocysteine, but there appeared to be no consistent relationship between by-pass and native concentrations. The calcium and phosphorus concentrations were relatively high in all cases, but the ratio of their molecular concentrations did not correspond to hydroxyapatite, which is conventionally considered to be the chemical form of calcium in heart plaque. In the mature native plaque, high calcium/phosphorus ratios indicated calcium in chemical forms other than hydroxyapatite. In undeveloped by-pass plaque, the phosphorus concentration was too high to be as hydroxyapatite but may be phospholipids. Because it is difficult to get suitable samples, only five heart samples were available. Therefore, these results should be treated as preliminary.


The effectiveness of group psychological intervention in enhancing perceptions of control following spinal cord injury.
This research investigated the effects of a structured psychological intervention, delivered during hospital rehabilitation, on the perceptions of control in people with spinal cord injury (SCI). A longitudinal study was designed to assess perceptions of control (using an objective measure of locus of control) in SCI persons who participated in specialised group cognitive-behavioural therapy (CBT) during hospital rehabilitation. The treatment SCI group's responses on locus of control were compared with a control group of SCI persons who only received traditional rehabilitation services during their hospitalisation. Mean locus of control scores were not high (i.e. external) for both groups and there were no overall group differences on locus of control responses across time in comparison to the control group. However, subjects in both groups who initially perceived life as externally controlled were extracted to form subgroups. The members of the subgroup who received CBT were significantly more likely to feel in control of themselves 2 years post injury compared to similar persons in the control group. Furthermore, an external locus of control was significantly but mildly associated with depressive mood 2 years after the injury. This research suggests that the provision of a structured psychological program in the rehabilitation stage will be beneficial for many SCI persons who feel that they have little control over their lives.


Optical Coherence Tomography for the Neurologist.
Optical coherence tomography (OCT) is a relatively new technology that is now routinely and very widely used by ophthalmologists for structural documentation of the optic nerve and retina. In neuro-ophthalmology and neurology, the value of OCT is ever expanding; its role in an increasing number of conditions is being reported in parallel with the advances of the technology. Currently, as a clinical tool, OCT is particularly useful for the structural measurement of peripapillary retinal nerve fiber layer thickness, optic nerve head volumetric analysis, and macular anatomy. Optic neuropathies of varied etiology (particularly from multiple sclerosis) may be the most common clinical indications for neurologists to obtain OCT imaging. Documentation and follow-up of disc edema of varied etiology (papilledema and idiopathic intracranial hypertension), discriminating true disc swelling from pseudopapilledema, and differentiating optic neuropathy from maculopathy are some other examples from clinical practice.


Healthier snacks in school vending machines: a pilot project in four Ontario high schools.
The Healthy Vending Machine Pilot Project (HVMPP) was a public health initiative intended to create a healthier school nutrition environment by making healthier snacks available in vending machines, while maintaining a profit margin. The HVMPP was evaluated using quantitative and qualitative measures. Vending machines were stocked with healthier choices and conventional vending products at a 50:50 ratio. The HVMPP was implemented from February to May 2007 in four Ontario secondary schools in Middlesex-London, Elgin, and Oxford counties. Product sales were tracked, and focus groups were conducted to obtain students' opinions about healthy eating and vending choices. "Healthier choice" sales ranged from 14% to 17%. In all schools, vending revenues declined from 0.7% to 66%. A majority of participants had substantial knowledge of healthy eating and were in favour of healthier choices in vending machines; however, price, value, and taste were barriers that led them to purchase these products rarely. Students preferred to have "real" healthy snacks, such as yogurt, fruit, and vegetables, available in schools. Replacing 50% of vending stock with healthier snacks resulted in a decline in vending revenues. Future health programs in schools need to provide "real" healthy snacks, such as low-fat dairy products, fruits, and vegetables.


Effect of H2 antagonists on the differential secretion of triamterene and its sulfate conjugate metabolite by the isolated perfused rat kidney.
The isolated perfused rat kidney model was used to examine the effect of the histamine H2 antagonists cimetidine, ranitidine, and famotidine and the organic anion inhibitor probenecid on the differential renal handling of triamterene and its active metabolite p-hydroxytriamterene sulfate. The kidneys were perfused with a Krebs-Henseleit buffer containing albumin, glucose, and amino acids to pH 7.4, and drug concentrations were measured by HPLC. At an initial triamterene concentration of 0.5 mg/liter, the unbound renal clearance to glomerular filtration rate (GFR) ratio was 11.0 +/- 2.5 (mean +/- SD): 1, indicating substantial tubular secretion of the drug. Cimetidine and ranitidine reduced the tubular secretion by about 80% (p less than 0.01), famotidine by between 35 and 60% (p = 0.05), whereas probenecid had no inhibitory effect. For p-hydroxytriamterene sulfate, its unbound renal clearance to GFR ratio was 41 +/- 25:1; this was not affected by cimetidine, ranitidine, or famotidine, whereas probenecid significantly (p less than 0.01) reduced the rate of tubular secretion by 80%. These data indicate that the renal tubular secretion of triamterene is mediated by the organic cation system, whereas for p-hydroxytriamterene sulfate its tubular secretion is via the organic anion system. Famotidine is a weaker inhibitor of the organic cation system compared with cimetidine and ranitidine. These results have implications for drug-drug interaction studies involving renal elimination pathways.


Development of a Tool to Assess the Team Leadership Skills of Medical Residents.
To develop a tool to assess the team leadership skills of internal medicine residents. A 27-item pilot instrument developed by two authors was distributed to interns on ward and intensive care unit teams at the end of rotations from a single institution's internal medicine residency program. These items were factor analyzed and reduced to a seven-item resident leadership scale (RLS). Validity of the instrument was assessed by comparing the rating on the RLS to scores on a validated measure of teaching skills provided at the same time and by the program director's global rating of team leadership skill for each resident at the completion of data collection. The three principal components from the factor analysis explained 82 percent of the variance. By introspection we reduced the scale to the final 7-item RLS that had a Cronbach alpha reliability estimate of 0.95. 490 ratings on 134 individual residents were available for analysis. The RLS scores correlated highly with both the validated measure of teaching skill and the program director's ratings. The RLS has robust psychometric properties. It may provide a useful tool for a broader assessment of trainee skill if validated in other settings.


NANETS/SNMMI Procedure Standard for Somatostatin Receptor-Based Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE.
With the recent approval of 177Lu-DOTATATE for use in gastroenteropancreatic neuroendocrine tumors, access to peptide receptor radionuclide therapy is increasing. Representatives from the North American Neuroendocrine Tumor Society and the Society of Nuclear Medicine and Molecular Imaging collaborated to develop a practical consensus guideline for the administration of 177Lu-DOTATATE. In this paper, we discuss patient screening, maintenance somatostatin analog therapy requirements, treatment location and room preparation, drug administration, and patient release as well as strategies for radiation safety, toxicity monitoring, management of potential complications, and follow-up. Controversies regarding the role of radiation dosimetry are discussed as well. This document is designed to provide practical guidance on how to safely treat patients with this therapy.


Prenatal diagnosis and postnatal findings of cephalothoracopagus janiceps disymmetros: a case report.
Conjoined twins are rare variants of monozygotic twins, which result from an incomplete division of the embryonic disk. Cephalothoracopagus is a rare twin pregnancy described as imperfect fusion of the head and chest, but separated columns, limbs, and pelvis. They occur with incidence rates that range from 1 per 50,000 to 1 per 100,000 births; however, the incidence of the cephalothoracopagus variety is 1 per 58 conjoined twins. In the case of identical and symmetric faces caused by the orientations of the 2 notochordal axes that are perfectly ventroventral, they are called janiceps disymmetros. We present a prenatal diagnosis of a typical case of cephalothoracopagus janiceps disymmetros and the diagnostic confirmation by image and pathology exams.


Regulation of PD-L1 expression in non-small cell lung cancer by interleukin-1β.
Programmed cell death-ligand 1 (PD-L1) is a biomarker for prediction of the clinical efficacy of immune checkpoint inhibitors in various cancer types. The role of cytokines in regulation of PD-L1 expression in tumor cells has not been fully characterized, however. Here we show that interleukin-1β (IL-1β) plays a key role in regulation of PD-L1 expression in non-small cell lung cancer (NSCLC). We performed comprehensive screening of cytokine gene expression in NSCLC tissue using available single-cell RNA-Sequence data. Then we examined the role of IL-1β in vitro to elucidate its induction of PD-L1 on NSCLC cells. The IL-1β gene is highly expressed in the tumor microenvironment, particularly in macrophages. The combination of IL-1β and interferon-γ (IFN-γ) induced a synergistic increase in PD-L1 expression in NSCLC cell lines. IL-1β and IFN-γ also cooperatively activated mitogen-activated protein kinase (MAPK) signaling and promoted the binding of downstream transcription factors to the PD-L1 gene promoter. Furthermore, inhibitors of MAPK signaling blocked upregulation of PD-L1 by IL-1β and IFN-γ. Our study reports high levels of IL-1β in the tumor microenvironment may cooperate with IFN-γ to induce maximal PD-L1 expression in tumor cells via activation of MAPK signaling, with the IL-1β-MAPK axis being a promising therapeutic target for attenuation of PD-L1-mediated suppression of antitumor immunity.


Pelvic lymphadenectomy for localized prostate cancer.
In the era of prostate specific antigen, there is increasing proportion of patients with localized prostate cancer. Accurate preoperative determination of lymph node status is important for adequate selection of treatment option, monitoring of response to treatment and early detection of recurrence. Lymph node invasion (LNI) is crucial prognostic parameter for patients who underwent curative treatment. Despite of continuous improvments of radiological armamentarium, CT, MRI and PET scans are not absolutely reliable in lymph node staging. Many nomograms have been developed for prediction of lymph node status, but accuracy of these statistical models is not better than 78%. Surgery, either open or laparoscopic pelvic lymphadenectmy (PLND), remains a cornerstone in lymph node staging. However, there are several controversies regarding PLND 1) necessity for routine perfoming in each patient, 2) anatomic boundaries for PLND, 3) morbidity of PLND, and 4) diagnostic and therapeutic value.


Cloning and expression of two crustacean hyperglycemic-hormone mRNAs in the eyestalk of the crayfish Orconectes limosus.
Crustacean hyperglycemic hormone (CHH) is a multifunctional neurohormone produced in the eyestalk of crustaceans and is primarily involved in the regulation of carbohydrate metabolism. In several crustacean species, CHH isoforms with identical amino acid sequences and molecular masses, but with different chromatographic elution patterns, are synthesized. To obtain sequence information on the CHH preprohormone in the crayfish Orconectes limosus we isolated two full-length cDNAs encoding two structurally different preproCHH species. The sequences of these precursors differ slightly in the signal peptide, the CHH-precursor-related peptide(CPRP)-coding sequences and in the non-coding regions, but are identical in the CHH peptide-coding sequence. Determination of the levels of preproCHH mRNAs and the amount of CHH peptide in the eyestalks of individual animals revealed that the ratio between the two preproCHH mRNAs varies for different individuals while the ratio between the two CHH peptide isoforms does not differ among animals. Our results suggest that the existence of two CHH isoforms in the crayfish O. limosus is due to a post-translational modification event. Northern-blot analysis showed only one band in eyestalk tissue with a size of approximately 2.4 kb, similar to the sizes of the cDNA sequences. Southern-blot analysis revealed the presence of at least two preproCHH genes in the crayfish suggesting a gene duplication event. Slight modifications in the duplicated genes could be responsible for the existence of the two preproCHH-encoding mRNAs.


Teaching of optics at an undergraduate college.
Being invited to participate in the symposium dedicated to John Strong of the Astronomy Research Facility of the University of Massachusetts and his 50 years in optics gives the author an opportunity to look back on his career and recall his roots while reviewing the teaching of optics at an undergraduate college in pre- and post-Sputnik days.


Electrical properties of phrenic motoneurons in the cat: correlation with inspiratory drive.
1. Resting membrane potential (Vmp), input resistance (Rn), rheobase (Irh), and after hyperpolarization duration (AHPdur) and amplitude (AHPamp) were measured in 38 phrenic motoneurons of anesthetized, paralyzed, and artificially ventilated cats during hypocapnic apnea. The mean +/- SD and range of values for these variables were as follows: Vmp, -68 +/- 5mV (range: -60 to -82); Rn, 1.3 +/- 0.6 M omega (0.6-2.4); Irh, 9.7 +/- 5 nA (2-20); AHPdur, 68 +/- 19 ms (37-134); AHPamp, 3.3 +/- 1.8 mV (1.0-8.5). In 31 motoneurons, the membrane potential level at which firing occurred (Vthr) during intracellular current injection was measured. The mean value of Vthr was -58 +/- 3 mV (range: -52 to -64). 2. A histogram of Rn revealed a bimodal distribution. Also a plot of Irh against Rn showed a grouping of the motoneurons into two subpopulations: 1) low-Rn and high-Irh cells, called type L neurons, and 2) high-Rn, low-Irh cells, called type H neurons. The overall negative linear correlation between Irh and Rn (r = -0.85; P less than 0.0001) resulted from this grouping rather than from a strictly linear relation between these two variables. 3. Electrical properties were compared for type L (n = 20) and type H (n = 18) phrenic motoneurons. The following mean values were found for each group, respectively: Rn, 0.8 and 1.8 M omega; Irh, 13.7 and 5.3 nA; AHPdur, 58 and 79 ms; AHPamp, 2.4 and 4.4 mV. All differences were significant (t test, P less than 0.001). Mean Vthr was the same for the two groups. 4. Comparison of these data with those available for lumbosacral motoneurons revealed that almost all investigated electrical properties of type L and type H phrenic motoneurons are similar to the analogous properties of type F (fast twitch) and type S (slow twitch) lumbosacral motoneurons, respectively. The apparent exception is the lower mean value of Irh for type L phrenic motoneurons compared with type F lumbosacral motoneurons. 5. For 13 cells, membrane potential was continuously monitored while spontaneous respiratory activity was restored by increasing CO2. It was found that at approximately the same end-tidal CO2 (about 7%) and a similar end-expiratory mean membrane potential level (approximately -70 mV), mean amplitude of peak inspiratory synaptic depolarization was higher in type H motoneurons (8.8 mV, n = 5) than in type L (2.9 mV, n = 8; P less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)


Effect of acetic acid deamidation-induced modification on functional and nutritional properties and conformation of wheat gluten.
Acids are often used for deamidating proteins, but the literature on acetic acid deamidation of proteins is sparse. Previous research on acetic acid-induced modification of proteins has focused on peptide proteolysis by relatively high concentrations of acetic acid (>1.5 mol L(-1)) rather than on the accompanying effect of deamidation. Therefore the objective of this study was to determine the deamidation effect of acetic acid with as little peptide proteolysis as possible by employing low-concentration acetic acid (<0.05 mol L(-1)) to deamidate wheat gluten. Changes in surface hydrophobicity, conformation, functional properties and nutritional characteristics of acetic acid-modified samples were determined and compared with those of hydrochloric acid (HCl)-modified samples. At similar degree of deamidation and nitrogen solubility index, samples deamidated with acetic acid showed less destruction of peptides bandings, better foaming properties and a more decompacted form (lower S--S content in protein as determined by Raman spectroscopy) than those deamidated with HCl and also exhibited improved emulsification capacity and emulsion stability compared with native wheat gluten. Acetic acid deamidation led to fewer changes in peptide molecular size and secondary structure of wheat gluten compared with HCl deamidation according to the results of sodium dodecyl sulfate polyacrylamide gel electrophoresis and Fourier transform infrared spectroscopy respectively. Amino acid analysis revealed that the nutritional characteristics of wheat gluten were well maintained after deamidation with acetic acid. The results show that low-concentration acetic acid can modify wheat gluten mainly by deamidation, resulting in deamidated wheat gluten with good functional and nutritional properties.


Reduction in toxicity for red blood cells in buffered solutions containing high concentrations of 2,3-butanediol by trehalose, sucrose, sorbitol, or mannitol.
Erythrocytes were stored at 4 degrees C in solutions of phosphate-buffered saline containing 2,3-butanediol and 4% (w/w) trehalose, sucrose, sorbitol, or mannitol. The 2,3-butanediol contained 96.7% (w/w) racemic mixture of the levo and dextro isomers and only 3.1% (w/w) of the meso isomer (2,3-butanediol 97% dl). The concentrations of 2,3-butanediol were 30 and 35% (w/w). A solution of 30% 2,3-butanediol showed relatively low toxicity. Hemolysis was only 2% after 5 h, but increased to 6% after 21 h and reached 60% after 46 h. Adding 4% (w/w) of one of the above compounds drastically decreased the toxicity. The two most efficient were the sugars trehalose and sucrose. With 30% 2,3-butanediol and 4% of any of the four compounds, hemolysis was about 0.6% after 2 days of storage. Furthermore, with trehalose or sucrose, hemolysis remained below 3% for 1 month. With sorbitol or mannitol, hemolysis slowly increased to 2% after 7 days and then increased rapidly. Even with 35% 2,3-butanediol, solutions containing trehalose or sucrose showed low toxicity. Hemolysis was also measured after redilution to buffered solution without 2,3-butanediol and without the additive, to mimic perfusion of organs with cryoprotectants and washing. Minima of hemolysis were observed after a few days of storage. The present solutions also have high glass-forming tendencies. They could be of great interest for organ vitrification.


Alcohol Use and Reasons for Drinking as Risk Factors for Suicidal Behavior in the U.S. Army.
High levels of alcohol use and alcohol-related problems are associated with suicidal behaviors (i.e., seriously considering and/or attempting suicide) in military and civilian populations. Examination of reasons for drinking alcohol may identify subgroups of soldiers who may either be at risk for suicidal behaviors or resilient to suicidality. We examined the associations among reasons for drinking, level of alcohol use, and past year suicidality in 3,813 U.S. Army soldiers using the Department of Defense Survey of Health-Related Behaviors among Active Duty Military Personnel. Six percent of soldiers reported suicidal thoughts and behaviors within the past year. Those who reported the highest level of alcohol use were more likely to have seriously considered and/or attempted suicide. Drinking to avoid rejection/"fit in" was associated with suicidality, even after adjusting for level of alcohol consumption, post-traumatic stress disorder, and depression. Although unadjusted analyses revealed a relation of pleasure-seeking drinking motives to suicidality, this association did not remain significant after controlling for covariates. Drinking to avoid rejection/"fit in" is associated with suicidality above overall alcohol consumption. Screening for this reason for drinking may be useful for suicide prediction and prevention.


Hydrostatic Pressure and Temperature Measurements Using an In-Line Mach-Zehnder Interferometer Based on a Two-Mode Highly Birefringent Microstructured Fiber.
We present a comprehensive study of an in-line Mach-Zehnder intermodal interferometer fabricated in a boron-doped two-mode highly birefringent microstructured fiber. We observed different interference signals at the output of the interferometer, related to the intermodal interference of the fundamental and the first order modes of the orthogonal polarizations and a beating of the polarimetric signal related to the difference in the group modal birefringence between the fundamental and the first order modes, respectively. The proposed interferometer was tested for measurements of hydrostatic pressure and temperature for different alignments of the input polarizer with no analyzer at the output. The sensitivities to hydrostatic pressure of the intermodal interference signals for x- and y-polarizations had an opposite sign and were equal to 0.229 nm/MPa and -0.179 nm/MPa, respectively, while the temperature sensitivities for both polarizations were similar and equal 0.020 nm/°C and 0.019 nm/°C. In the case of pressure, for the simultaneous excitation of both polarization modes, we observed a displacement of intermodal fringes with a sensitivity depending on the azimuth of the input polarization state, as well as on the displacement of their envelope with a sensitivity of 2.14 nm/MPa, accompanied by a change in the fringes visibility. Such properties of the proposed interferometer allow for convenient adjustments to the pressure sensitivity of the intermodal fringes and possible applications for the simultaneous interrogation of temperature and pressure.


Pain management of nalbuphine and sufentanil in patients admitted intensive care unit of different ages.
Pain relief for patients in the intensive care unit (ICU) can improve treatment outcomes and reduce the burden on doctors and nurses. This study aims to report the clinical analgesic and sedative effects of nalbuphine and sufentanil on ICU patients. This study retrospectively analyzed the medical records of 87 critically ill patients who received nalbuphine or sufentanil infusion in the ICU, including demographic data, diagnosis, Acute Physiology and Chronic Health Evaluation (APACHE) II, Critical Care Pain Observation Tool (CPOT), Richmond Agitation-Sedation Scale (RASS), systolic and diastolic blood pressure, heart rate and blood oxygen saturation (SpO2). The primary outcomes of this study were CPOT and RASS scores. The secondary outcomes were hemodynamic changes, including systolic blood pressure, diastolic blood pressure, heart rate, and SpO2. The adverse events recorded during pain management, such as hypoxemia, respiration depression and bradycardia, were also collected and analyzed. None of the patients in both groups experienced episode of hypoxemia, respiration depression and bradycardia. However, age-stratified analyses showed that nalbuphine has a better analgesic effect than sufentanil for patients aged ≤ 60 (P < 0.05). In contrast, sufentanil showed a better analgesic effect than nalbuphine for patients aged > 60 ( P < 0.05). Furthermore, nalbuphine has a significantly better sedative effect than sufentanil for patients aged ≤ 60 (P < 0.05). ICU patients of different age groups may be suitable for different analgesics. For patients under the age of 60, nalbuphine has better analgesia and sedation than sufentanil, and does not cause respiratory depression and drastic hemodynamic changes.


Effect of intravitreal injection of ranibizumab on retinal ganglion cells and microvessels in the early stage of diabetic retinopathy in rats with streptozotocin-induced diabetes.
The aim of the present study was to investigate the effect of intravitreal injection of ranibizumab on retinal ganglion cells and microvessels at the early stage of diabetic retinopathy (DR) in rats with streptozotocin-induced diabetes mellitus (DM). DM was induced by a single intraperitoneal injection of 60 mg/kg body weight streptozotocin. A total of 80 diabetic rats were randomly assigned to four treatment groups (n=20 in each group) and were treated with an oculus dexter intravitreal injection of ranibizumab. Groups A and B were injected with ranibizumab two and four weeks after DM-induction, respectively, while groups a and b (controls) were injected with phosphate-buffered saline at the same time points. In addition, 20 normal rats were assigned to group N (blank control; without intraocular injection). Vitreous humors were isolated for vascular endothelial growth factor (VEGF)-A ELISA and retinas were obtained for hematoxylin and eosin staining, periodic acid-Schiff staining and fluorescence imaging techniques at six and eight weeks after the onset of DM. At six and eight weeks, a significantly increased in retinal ganglion cells (RGCs) was observed in group A compared with group a (P<0.01), and in group B compared with group b (P<0.01). In addition, there was a significant difference in the RGC level between groups A and B at six weeks after DM induction (P<0.01), but not at eight weeks (P>0.05). VEGF-A concentrations in rat vitreous humors were significantly lower in groups A and B compared with groups a and b at six and eight weeks after DM induction (P<0.01). Furthermore, the ratio of endotheliocytes to pericytes in groups A and B was significantly lower compared with groups a and b at six and eight weeks (P<0.05). Furthermore, it was also demonstrated that type IV collagen-positive strands were not present in group A during the eight-week observation period, which was significantly different from groups a, b and B (P<0.01). In conclusion, intravitreal injection of ranibizumab at a very early stage of DR in streptozotocin-induced DM rats slowed the progression of DR by reducing vascular regression or damage and maintaining RGC numbers, as well as reducing VEGF-A concentrations.


Fungemia due to Trichosporon mucoides in a diabetes mellitus patient: a rare case report.
Trichosporon species are widely distributed in nature and can occasionally belong to the human microbiota. For many years, Trichosporon beigelii, the only species of this genus, was found as the aetiological agent of superficial skin infection called white piedra. However, many cases of invasive trichosporonosis caused by different newly delineated species of Trichosporon have been published in increasing numbers in recent past years, especially in immunocompromised persons. We report a rare case of fungemia due to Trichosporon mucoides in a diabetes mellitus patient, which will add to the emerging list of trichosporonosis infections.


Amphiphilic Polyampholytes for Fouling-Resistant and Easily Tunable Membranes.
The versatility of membranes is limited by the narrow range of material chemistries on the market, which cannot address many relevant separations. Expanding their use requires new membrane materials that can be tuned to address separations by providing the desired selectivity and robustness. Self-assembly is a versatile and scalable approach to create tunable membranes with a narrow pore size distribution. This study reports the first examples of a new class of membrane materials that derives state-of-the-art permeability, selectivity, and fouling resistance from the self-assembly of random polyampholyte amphiphilic copolymers. These membranes feature a network of ionic nanodomains that serve as nanochannels for water permeation, framed by hydrophobic nanodomains that preserve their structural integrity. This copolymer design approach enables precise selectivity control. For example, sodium sulfate rejections can be tuned from 5% to 93% with no significant change in the pore size or fouling resistance. Membranes developed here have potential applications in wastewater treatment and chemical separations.


Fine-Tuning Apertures of Metal-Organic Cages: Encapsulation of Carbon Dioxide in Solution and Solid State.
Metal-organic cages are potential artificial models for mimicking biological functions due to their capability of selective encapsulation for certain guest molecules. In this work, we designed and synthesized a series of rhombic dodecahedral Ni-imidazolate cages (Ni14L24) with precisely controlled aperture for CO2 encapsulation. The aperture of the cages can be tuned by the strategies of ligand decoration and metal-ion hybridization. Similar to the breathing function of alveoli, CO2 passes through the dynamic aperture into the cages under a pressure of 2.0-3.0 bar in methanol solution, and slowly move out of the cages when the pressure goes down. In the solid state, CO2 is encapsulated and prisoned in the cages under a high pressure of 15.0-30.0 bar or supercritical conditions. By replacing the square-coordinated Ni2+ with Cu2+, the resulting Ni-Cu heteronuclear cage lost the capability of physically encapsulating CO2 even though the aperture's size is only slightly changed.


Validity and reliability of autofluorescence-based quantification method of dental plaque.
The aim of this study was to evaluate validity and reliability of autofluorescence-based plaque quantification (APQ) method. The facial surfaces of 600 sound anterior teeth of 50 subjects were examined. The subjects received dental plaque examination using Turesky modified Quigley Hein plaque index (QHI) and Silness & Löe plaque index (SLI). The autofluorescence images were taken before the plaque examination with Quantitative Light-induced Fluorescence-Digital, and plaque percent index (PPI) was calculated. Correlation between two existing plaque indices and the PPI of the APQ method was evaluated to find which level of plaque redness on tooth (ΔR) by the APQ method shows the highest correlation. The area under the ROC curve (AUC) analysis and intra- and inter-examiner reliability tests were performed. The PPIΔR20 of the APQ method showed a moderate correlation with two existing plaque indices (rho of QHI=0.48, SLI=0.51). This methodology fell in the fair category and it had an excellent reliability. The APQ method also showed possibility to detect heavy plaque with fair validity. The APQ method demonstrated excellent reliability, and fair validity, compared with 2 conventional indices. The plaque quantification described has the potential to be used in clinical evaluation of oral hygiene procedures.


Permanent outdoor housing for woodchucks, Marmota monax.
Permanent outdoor housing for woodchucks (Marmota monax) was constructed from chain link fencing sections on a concrete base. Metal poultry nest boxes were attached to 1 side of the cage. Each enclosure accommodated up to 10 woodchucks and provided adequate shelter and exercise space. This housing system was inexpensive to construct and efficient to service.


Changes in messenger ribonucleic acid encoding luteinizing hormone receptor, cytochrome P450-side chain cleavage, and aromatase are associated with recruitment and selection of bovine ovarian follicles.
The objective of this study was to investigate changes in expression of mRNAs encoding FSH receptor (FSHr), LH receptor (LHr), cytochrome P450 side-chain cleavage (P450(scc)), cytochrome P450 17alpha-hydroxylase (P450(c17)), and cytochrome P450 aromatase (P450(arom)) during recruitment and selection of bovine ovarian follicles. Dairy heifers (4-5 per group) were ovariectomized at 12, 24, 36, 48, 60, 72, 84, or 96 h after initiation of the first follicular wave following estrus as determined by ultrasonography (Time 0 = initiation of follicular wave; mean +/- SEM = 42.0 +/- 2.6 h after estrus). Expression of mRNAs encoding FSHr, LHr, P450(scc), P450(c17), and P450(arom) was detected by in situ hybridization and quantified by image analysis. Antral follicles were classified as healthy or atretic. Healthy follicles expressed higher (p < 0.01) amounts of mRNAs for gonadotropin receptors and steroidogenic enzymes than did atretic follicles, and expression of LHr, FSHr, P450(scc), P450(c17), and P450(arom) increased (p < 0.01) with follicular size and stage of the follicular wave. Expression of mRNAs for P450(scc), P450(arom), and LHr was time- and size-dependent during recruitment and selection. During recruitment, expression of mRNAs for P450(scc) and P450(arom) was first detected in granulosa cells of 16 of 21 of the follicles 4-6 mm in diameter at 12 h. At 24 and 36 h, almost all follicles 6-9 mm in diameter, but not those 4-5 mm in diameter, expressed both P450(scc) and P450(arom) mRNA in the granulosa cells. At 48 h and thereafter, P450(scc) and P450(arom) mRNA were expressed predominantly in one healthy large follicle per cow with a few exceptions. Expression of LHr mRNA was first detected in granulosa cells at 36 h and was always found in granulosa cells of one follicle > or = 8 mm per cow with exception of one cow at 36 h (no expression) and another two cows, one each at 36 and at 84 h (expression in 2 follicles). In addition, LHr mRNA expression in the granulosa cell layer was limited to follicles that also expressed mRNAs for P450(scc) and P450(arom) in the granulosa cells. In summary, follicular recruitment in cattle was associated with expression of P450(scc) and P450(arom) mRNA within granulosa cells, and the process of follicular selection was associated with initiation of LHr mRNA expression in granulosa cells.


Evaluation of Skeletal Muscle Microcirculation and Reserve Function of the Type 2 Diabetes with Contrast-Enhanced Ultrasonography.
This study aimed to discuss clinical application value of contrast-enhanced ultrasonography on lesion skeletal muscle microcirculation and arterial perfusion reserve in type 2 diabetes mellitus and complicated microvessels. Patients in the control group, type 2 diabetes mellitus (DM) group, diabetic microangiopathy (DM + MC) group underwent contrast-enhanced ultrasonography before and after temporary arterial occlusion to observe blood perfusion of gastrocnemius muscle; draw the time-intensity curve of arteriole, muscular tissue, and venule, and obtain perfusion parameters such as contrast agent arrival time and contrast agent transit time. Blood glucose, insulin, insulin resistance index, and relevant blood rheology parameters were measured. Contrast agent transit time of the DM + MC group before arterial occlusion was significantly longer than that of the DM group and control group (P < 0.05). Contrast agent transit time of the DM + MC group after temporary arterial occlusion was significantly longer than that of the DM group and control group (P < 0.05). Contrast agent transit time of △artery-muscle, △artery-vein, and △muscle-vein of the DM group and control group and △artery-muscle of the DM + MC group after arterial occlusion was significantly shortened, when compared with that before arterial occlusion (P < 0.05). For △muscle-vein and △artery-vein contrast agent transit time in the DM + MC group, the difference was not statistically significant. By comparing blood glucose, insulin, insulin resistance index, and relevant blood rheology parameters among the DM + MC group, DM group, and control group, the difference was statistically significant, and there was a good correlation. Contrast-enhanced ultrasonography can be used to evaluate skeletal muscle microcirculation disturbance and arterial reserve function of patients who had type 2 diabetic microangiopathy.


Analysis of the Mechanism of RAD18 in Glioma.
This study aimed to evaluate the regulatory mechanism of RAD18 in glioma development. RAD18 expression was compared in glioma tumors and normal samples. Furthermore, we investigated the association between gene transcription and clinical factors in glioma samples, followed by functional enrichment analysis, screening for key Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, immune infiltration analysis of high and low RAD18 expression groups, and correlation analysis of quantified KEGG signaling pathways and immune cell types. The expression of RAD18 was upregulated in gliomas. Moreover, RAD18 expression was significantly correlated with age, tumor grade, and histological subtype. Notably, patients with gliomas with high RAD18 expression levels had worse overall survival. Functional enrichment analysis showed that RAD18 was significantly related to biological processes, such as cell division, chemical synaptic transmission, and mitotic nuclear division, and KEGG pathways such as cell cycle, oxidative phosphorylation, and extracellular matrix (ECM)-receptor interaction. The infiltration of five immune cells (plasma B cells, naive B cells, resting CD4+ memory T cells, monocytes, and M1 macrophages) was significantly different between the high and low RAD18 expression groups, and this difference was significantly related to key KEGG pathways, such as neuroactive ligand-receptor interaction and ECM-receptor interaction. RAD18 may serve as a target for glioma treatment and as a key regulator of glioma development.


[Effect of dexamethasone on osteopontin expression in the lung tissue of asthmatic mice].
To study the correlation between airway inflammation and osteopontin (OPN) level in the lung tissue, and to study the effect of dexamethasone (DXM) on OPN expression. Fifty mice were randomly divided into 5 groups: normal control, ovalbumin (OVA)-challenged asthma groups (OVA inhalation for 1 week or 2 weeks) and DXM-treated asthma groups (DXM treatment for 1 week or 2 weeks). The mice were sensitized and challenged with OVA to prepare mouse model of acute asthma. Alterations of airway inflammation were observed by haematoxylin-eosin staining. Serum level of OVA-sIgE was evaluated using ELISA. OPN expression in the lung tissue was located and measured by immunohistochemistry and Western blot respectively. OPN mRNA level in the lung tissue was detected by real-time PCR. The asthma groups showed more pathological changes in the airway than the normal control and the DXM-treated groups. Compared with the OVA-challenged 1 week group, the pathological alterations increased in the OVA-challenged 2 weeks group. The level of OVA-sIgE in serum increased in the asthma groups compared with the control and the DXM groups (P<0.01). Serum OVA-sIgE sevel increased more significantly in the OVA-challenged 2 weeks group compared with the OVA-challenged 1 week group (P<0.01). OPN protein and mRNA levels were significantly raised in the asthma groups compared with the normal control and the DXM groups (P<0.01), and both levels increased more significantly in the OVA-challenged 2 weeks group compared with the OVA-challenged 1 week group (P<0.01). The increased OPN expression in the lung tissue is associated with more severe airway inflammation in asthmatic mice, suggesting that OPN may play an important role in the pathogenesis of asthma. DXM can alleviate airway inflammation possibly by inhibiting OPN production.


Clinical, Biochemical, Radiological, and Genetic Profile of Patients with Homocysteine Remethylation Pathway Defect and Spastic Paraplegia.
The objective of this study is to describe the clinical, biochemical, radiological, and genetic profile of patients presenting with progressive spastic paraparesis due to homocysteine remethylation pathway defect. This was a retrospective study conducted by reviewing the medical records of patients with serum homocysteine levels >50 μmol/L between January 2015 and January 2019 at our hospital. We included patients presenting with progressive spastic paraparesis, having serum homocysteine >50 μmol/L with low or normal blood methionine suggesting disorders of homocysteine remethylation. Demographic details, clinical manifestations, biochemical abnormalities, neuroimaging findings, and genetic profile were analyzed. A total of seven patients (M: F = 5:2) fulfilled the study eligibility criteria. The mean age at onset of the disease was 13.4 ± 2.4 years (range: 9-17 years). Spastic paraparesis was the presenting manifestation in 4/7 (57.1%) patients. Other manifestations included cognitive decline, poor scholastic performance, behavioral disturbances, seizures, and spastic bladder. Severe hyperhomocysteinemia (>100 μmol/L) was noted in 6/7 (85.7%) patients with median levels of serum homocysteine being 185.7 μmol/L (range: 85.78-338.5 μmol/L). Neuroimaging showed parieto-occipital predominant leukoencephalopathy in 5/7 (71.4%) and diffuse cerebral atrophy in 1/7 (14.2%). Genetic analysis in three patients revealed pathogenic missense variants c.459C >G (p.Ile153Met), c.973C >T (p.Arg325Cys), and c.1031G >T (p.Arg344Met) in MTHFR gene. All the patients received vitamin B12 (injection and oral), folic acid, and pyridoxine and two patients received betaine. At the last follow-up of a median duration of 12 months, there was a good clinical and biochemical response with reduction in the median value of serum homocysteine by 77.5 μmol/L. Evaluation of serum homocysteine and blood methionine in adolescents presenting with progressive spastic paraparesis gives clue to a treatable homocysteine remethylation disorders.


The new biologics in pregnancy.
Growing numbers of women of reproductive age are prescribed new biological agents. This is resulting in more pregnancies exposed to these drugs. What are the new biologics (also referred to as biologicals) and what are their indications? How are they currently used in pregnant women? What are the concerns when treating pregnant women with biologics? What do we know about the reproductive safety of these agents? Current and future research is discussed.


Medium-sized double magic metal clusters: Al@Cu(54) (-) and Al@Ag(54) (-).
Medium-sized double magic metal clusters, Al@Ag(54) (-) and Al@Cu(54) (-), are predicted based on unbiased global search and density functional calculation. Both bimetallic core-shell clusters have icosahedral symmetry, and they are much lower in energies than all other low-lying isomers. In contrast, the icosahedral cluster Al@Au(54) (-) is a high-energy isomer. Both Al@Ag(54) (-) and Al@Cu(54) (-) exhibit appreciable gaps between the highest occupied molecular orbital and the lowest unoccupied molecular orbital, and strong spherical aromaticity, which provide two additional evidences for the likelihood of their high stability. The simulated anion photoelectron spectra and optical absorption spectra are readily compared with future experiments.


The clinical characteristics and treatment of cerebral AVM in pregnancy.
Cerebral arteriovenous malformation (AVM) in pregnancy is a complex situation and there is no agreement on its hemorrhage risk and treatment. Although studies on bleeding risk of cerebral AVMs in pregnancy are very few and there are different results between them, pregnancy will increase the hemorrhagic risk of AVM, and ruptured cerebral AVM in pregnancy should be treated actively. After intracranial hemorrhage, cerebral angiography should be performed for pregnant women shielded correctly. Cerebral angiography could clearly demonstrate the characteristics of cerebral AVM. The results from the literature show that the radiation dose of endovascular and stereotactic radiotherapy for cerebral AVM in pregnancy is below the safety value and is safe. Unruptured AVM in pregnancy, if there is no bleeding factor, such as no coexisting aneurysm, smooth venous drainage, no venous ectasia, or high risk of treatment, should be observed conservatively.


Mitomycin C plus cisplatin for systemic treatment of recurrent BRCA1-associated ovarian cancer.
Background Previous studies on neoadjuvant therapy for BRCA1-driven ovarian cancer (OC) demonstrated higher efficacy of mitomycin C plus cisplatin combination as compared to standard drug schemes. These data call for evaluation of the utility of this regimen for the treatment of recurrent BRCA1-associated OC. Methods The study included 12 BRCA1 germ-line mutation carriers, whose disease relapsed after one (n = 4) or two (n = 8) lines of chemotherapy. The patients received cisplatin 100 mg/m2 and mitomycin C 10 mg/m2, given every four weeks, for 6 (n = 10), 8 (n = 1) or 5 (n = 1) cycles. Retrospective data on conventional treatment of OC relapses in BRCA1 heterozygotes (n = 47) served as a control. Results Grade 3-4 toxicities were observed in 4/12 (33%) cases. There were 6 complete responses (CR), 4 partial responses (PR) and 2 instances of stable disease (SD). Comparison of patients receiving mitomycin C plus cisplatin (n = 4) or conventional therapy (n = 44) at first relapse demonstrated marginal improvement of the progression-free survival (PFS) (16.6 months vs. 10.2 months, P = .067). Use of mitomycin C plus cisplatin (n = 8) for the treatment of second relapse resulted in significant prolongation of PFS as compared to standard regimens (n = 31) (14.8 months vs. 4.8 months, P = .002). Conclusions Mitomycin C plus cisplatin shows promising activity in recurrent BRCA1-driven ovarian cancer.